AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a sy...AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk(AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.展开更多
We studied 14 moderately overweight Typo 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period , and again after 3 months of antihypertensive treatment with the angiotensin-...We studied 14 moderately overweight Typo 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period , and again after 3 months of antihypertensive treatment with the angiotensin-converting enzyme (ACF) inhibitor captopril. Glucose tolerance was tested with a 75g oral glucose load (OGTT) and insulin sensitivity was measured by the insulin suppression test (IST) while dietary and drug treatment of the hyperglycemia was maintained constant. In the whole group. mean blood pressure (MBP) fell progressively over 3months from a baseline value of 123± 3 mmHg (1 mmHg= 0. 133 kpa) to a final value of 115± 2 mmHg(P<0. 005). After treatment, fasting plasma glucose, insulin, free fatty acid (FFA). potassium, and glycosylated hemoglobin concentrations were unchanged from baseline. There were no significant differences in glucose tolerance and insulin sensitivity between pre- and post-trearment values. Neither endogenous (oral glucose) nor exogenous (IST) insulin caused any change in plasma potassium concentration. This resistance to the hypokalemic action of insulin was not affected by captopril.展开更多
Anoectochilus chapaensis Gagnep. （Orchidaceae）, an indigenous and valuable Chinese folk medicine, has been widely used in China to treat diabetes. However, few reports are available about its constituents and activi...Anoectochilus chapaensis Gagnep. （Orchidaceae）, an indigenous and valuable Chinese folk medicine, has been widely used in China to treat diabetes. However, few reports are available about its constituents and activity. The present experiment was conducted to investigate the active fractions from A. chapaensis in diabetic rat model induced by high-fat diet plus streptozotocin. The total EtOH extract from the whole herbs ofA. chapaensis, half of which was partitioned in sequence with petrol ether （PE）, ethyl acetate （EtOAc）, n-BuOH and H2O, thus yielding four fractions, all of them were orally administered with an identical dose amount to 4 g/kg dried crude herbs once a day for consecutive two weeks to further investigate the antihyperglycemic activity. The EtOAc fraction caused a significant fall in the non-fasting blood glucose level of diabetic rats from （402.66±82.26） to （226.26±62.10） mg/dl, which may be attributed to ameliorating insulin resistance, modulating the activity of enzymatic antioxidants, reducing the content of NO, etc. Much more intact β cells in the islets of Langerhans in EtOAc fraction-treated groups than the negative control were observed, which greatly supported the morphological and functional elucidation. The OGTT evidenced that EtOAc fraction could promote the endurance capacity of acute glucose increase in diabetic rats. The EtOAc fraction of A. chapaensis contains some hypoglycemic and antioxidant principles with the potential to be developed further for the treatment of diabetes specifically associated with an insulin resistance state.展开更多
OBJECTIVE： To explore the effect of electroacu- puncture and Chinese kidney-nourishing medicine on insulin （INS）, adiponectin （APN）, leptin （LEP）, and glucolipid metabolism of obese patients with polycystic ova...OBJECTIVE： To explore the effect of electroacu- puncture and Chinese kidney-nourishing medicine on insulin （INS）, adiponectin （APN）, leptin （LEP）, and glucolipid metabolism of obese patients with polycystic ovary syndrome （PCOS）. METHODS： Sixty-seven obese PCOS patients were randomly divided into two groups. Thirty-three pa- tients in the acupuncture-medicine group were treated three times a week with electroacupunc- ture at the Tianshu （ST 25）, Zhongwan （CV ] 2）, Qi- hai （CV 6）, Sanyinjiao （SP 6）, Geshu （BL 17）, and Cil-iao （BL 32） acupoints. They drug, Tiankui capsule, for 3 treatment. Point-taking and also took the Chinese months as a course of treatment in the elec- troacupuncture group of 34 patients was the same as those in the acupuncture-medicine group. We observed and compared the changes in the obesi- ty-related indexes of body weight （BW）, body mass index （BMI）, and waist-hip ratio （WHR）, as well as fasting plasma glucose （FPG）, fasting insulin （FINS）, APN, and LER RESULTS： BW, BMI, WHR, and FINS decreased and insulin sensitivity index （ISI） and APN were higher in the acupuncture-medicine group than in the electroacupuncture group （P〈0.01）. There was no obvious difference in LEP between the two groups （P〉0.05）. CONCLUSION： Acupuncture combined with medi- cine is better than just electroacupuncture for obese PCOS patients by improving obesity-related indexes, insulin sensitivity, and APN level. This indi- cates that acupuncture-medicine therapy is worth clinical popularization.展开更多
基金Supported by A grant from Innovative Research Institute for Cell Therapy Project,South Korea,No.A062260
文摘AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk(AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.
文摘We studied 14 moderately overweight Typo 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period , and again after 3 months of antihypertensive treatment with the angiotensin-converting enzyme (ACF) inhibitor captopril. Glucose tolerance was tested with a 75g oral glucose load (OGTT) and insulin sensitivity was measured by the insulin suppression test (IST) while dietary and drug treatment of the hyperglycemia was maintained constant. In the whole group. mean blood pressure (MBP) fell progressively over 3months from a baseline value of 123± 3 mmHg (1 mmHg= 0. 133 kpa) to a final value of 115± 2 mmHg(P<0. 005). After treatment, fasting plasma glucose, insulin, free fatty acid (FFA). potassium, and glycosylated hemoglobin concentrations were unchanged from baseline. There were no significant differences in glucose tolerance and insulin sensitivity between pre- and post-trearment values. Neither endogenous (oral glucose) nor exogenous (IST) insulin caused any change in plasma potassium concentration. This resistance to the hypokalemic action of insulin was not affected by captopril.
基金National Natural Science Foundation of China(Grant No.81001628)Guangdong Natural Science Foundation(Grant No.S2013010014771)
文摘Anoectochilus chapaensis Gagnep. （Orchidaceae）, an indigenous and valuable Chinese folk medicine, has been widely used in China to treat diabetes. However, few reports are available about its constituents and activity. The present experiment was conducted to investigate the active fractions from A. chapaensis in diabetic rat model induced by high-fat diet plus streptozotocin. The total EtOH extract from the whole herbs ofA. chapaensis, half of which was partitioned in sequence with petrol ether （PE）, ethyl acetate （EtOAc）, n-BuOH and H2O, thus yielding four fractions, all of them were orally administered with an identical dose amount to 4 g/kg dried crude herbs once a day for consecutive two weeks to further investigate the antihyperglycemic activity. The EtOAc fraction caused a significant fall in the non-fasting blood glucose level of diabetic rats from （402.66±82.26） to （226.26±62.10） mg/dl, which may be attributed to ameliorating insulin resistance, modulating the activity of enzymatic antioxidants, reducing the content of NO, etc. Much more intact β cells in the islets of Langerhans in EtOAc fraction-treated groups than the negative control were observed, which greatly supported the morphological and functional elucidation. The OGTT evidenced that EtOAc fraction could promote the endurance capacity of acute glucose increase in diabetic rats. The EtOAc fraction of A. chapaensis contains some hypoglycemic and antioxidant principles with the potential to be developed further for the treatment of diabetes specifically associated with an insulin resistance state.
基金Supported by the National Basic Research Program of China(973 program,No.2009CB522900)Open Research Fund of Zhejiang First-foremost Key Subject-Acupuncture and Moxibustion(No.ZTK2010B02)Shanghai Municipal Health Bureau(No.20124049)
文摘OBJECTIVE： To explore the effect of electroacu- puncture and Chinese kidney-nourishing medicine on insulin （INS）, adiponectin （APN）, leptin （LEP）, and glucolipid metabolism of obese patients with polycystic ovary syndrome （PCOS）. METHODS： Sixty-seven obese PCOS patients were randomly divided into two groups. Thirty-three pa- tients in the acupuncture-medicine group were treated three times a week with electroacupunc- ture at the Tianshu （ST 25）, Zhongwan （CV ] 2）, Qi- hai （CV 6）, Sanyinjiao （SP 6）, Geshu （BL 17）, and Cil-iao （BL 32） acupoints. They drug, Tiankui capsule, for 3 treatment. Point-taking and also took the Chinese months as a course of treatment in the elec- troacupuncture group of 34 patients was the same as those in the acupuncture-medicine group. We observed and compared the changes in the obesi- ty-related indexes of body weight （BW）, body mass index （BMI）, and waist-hip ratio （WHR）, as well as fasting plasma glucose （FPG）, fasting insulin （FINS）, APN, and LER RESULTS： BW, BMI, WHR, and FINS decreased and insulin sensitivity index （ISI） and APN were higher in the acupuncture-medicine group than in the electroacupuncture group （P〈0.01）. There was no obvious difference in LEP between the two groups （P〉0.05）. CONCLUSION： Acupuncture combined with medi- cine is better than just electroacupuncture for obese PCOS patients by improving obesity-related indexes, insulin sensitivity, and APN level. This indi- cates that acupuncture-medicine therapy is worth clinical popularization.
